Biomedical subjects

T E Adrian

Publications and source records attributed to T E Adrian.

At least 127 records · Page 7Linked to original sources

PubMed1993

Islet amyloid polypeptide in the rabbit and European hare: studies on its relationship to amyloidogenesis.

In this study, we determined the cDNA-predicted amino acid sequence of positions 9-31 of islet amyloid polypeptide from the rabbit and European hare. A synthetic rabbit/hare islet amyloid polypeptide 20-29 peptide was subsequently shown to be strongly fibrillogenic in vitro even though the putative amyloidogenic AILS sequence at positions 25-28 of human and cat islet amyloid polypeptide is modified in the rabbit and hare by a substitution of phenylalanine for leucine at position 27 (i.e. AIFS). Although islet amyloid polypeptide of both the rabbit and hare has an amyloidogenic sequence and is in fact amyloidogenic in vitro, the apparent lack of in vivo islet amyloidosis in rabbits and hares may be related to relatively low levels of islet amyloid polypeptide production by the islet beta cells in these species. This was supported by our findings that there is no substantial immunoreactivity in either rabbit or hare islets, and no measurable amount either in extracts of rabbit pancreases, or in rabbit plasma. This study supports the need for at least two prerequisites for the development of islet amyloidosis in vivo: an inherent fibrillogenic sequence within the islet amyloid polypeptide molecule and an adequate local concentration of islet amyloid polypeptide to promote self aggregation and formation of islet amyloid.

Amino Acid Sequence↗

PubMed1993

Effect of graded exercise on esophageal motility and gastroesophageal reflux in trained athletes.

We evaluated the effect of graded exercise on esophageal motility and gastroesophageal reflux. We studied eight trained cyclists using a catheter with three strain-gauge transducers connected to a solid-state datalogger and an ambulatory intraesophageal pH monitor. Each study lasted 4 hr during which subjects exercised on a stationary bike for 1 hr at 60% of peak O2 uptake (O2 max), 45 min at 75% of O2 max, and for 10 min at 90% of O2 max. Subjects rested 1 hr before exercise (control period) and for 30 min between exercise sessions. Studies were performed after an overnight fast and subjects received only intravenous infusion of 5% glucose solution during the study. Plasma concentrations of gastrin, motilin, glucagon, pancreatic polypeptide (PP), and vasoactive intestinal peptide (VIP) were determined at rest and before and after each exercise session. The duration, amplitude, and frequency of esophageal contractions declined with increasing exercise intensity, and the differences were significant (P < or = 0.05) for all three variables at 90% O2 max. The number of gastroesophageal reflux episodes and the duration of esophageal acid exposure were significantly (P < or = 0.05) increased during exercise at 90% O2 max. Plasma hormone concentrations showed no significant changes between rest and the various exercise sessions. Thus, exercise has profound effects on esophageal contractions and gastroesophageal reflux which are intensity dependent. These effects are not mediated by the hormones measured.

Adult↗

PubMed1993

Postnatal development of circulating cholecystokinin and secretin, pancreatic growth, and exocrine function in guinea pigs.

Concentrations of cholecystokinin (CCK) and secretin from neonatal guinea pig plasma were evaluated in relation to pancreatic growth, and secretion from dispersed pancreatic acini. Plasma CCK was low at birth (3.1 +/- 0.8 pmol/L) but rose markedly by day 15 (11.0 +/- 0.8 pmol/L, p < 0.001). Plasma secretin was also low at birth (3.8 +/- 0.8 pmol/L) but peaked on day 4 (17.0 +/- 1.4 pmol/L, p < 0.001) and remained elevated through d 15. Adult nonfasting plasma CCK and secretin levels were 12.3 +/- 0.8 and 8.9 +/- 1.5 pmol/L, respectively. Pancreatic weight more than doubled during the first week of life, with the greatest increase during the first 4 d (156 +/- 4 to 262 +/- 10 mg/100g body wt, p < 0.001). Body weight increased most dramatically during the second week (126 +/- 9 to 190 +/- 7 g p < 0.001). Amylase secretion from isolated acini stimulated by CCK-8, carbachol, phorbol ester, forskolin, and calcium ionophore (A23187) was present at birth. The percentage of total amylase content secreted in response to CCK, carbamylcholine, and secretin did not change during the first 2 wk of neonatal life, and was independent of surges in circulating CCK and secretin. These results indicate that functional maturity of the guinea pig pancreas for amylase secretion occurs early and is different from the rat, mouse, pig, and human. Since results can readily be compared between animals of different postnatal ages, the neonatal guinea pig is ideally suited for the study of hormonal effects on acinar cell function.

Amylases↗

PubMed1993

Peptide YY is a physiological regulator of water and electrolyte absorption in the canine small bowel in vivo.

BACKGROUND: Peptide YY (PYY), a hormone released following a meal, is one potential mediator of intestinal absorption. Although PYY inhibits 5'-cyclic adenosine monophosphate (cAMP)-stimulated small intestinal secretion in vitro, its effects on fluid and electrolyte transport in vivo are unknown. METHODS: This study examines the effects of physiological doses of PYY in dogs (n = 6) with jejunal and ileal exteriorized, neurovascularly intact intestinal loops (Thiry-Vella fistulas). RESULTS: Plasma PYY levels increased after a meal from 155 +/- 15 to 324 +/- 26 pmol/L at 30 minutes and remained elevated for 2 hours. PYY infused intravenously in unfed animals at 25, 50, 100, and 200 pmol.kg-1.h-1, produced a dose-dependent increase in plasma PYY levels. At 100 pmol.kg-1.h-1, PYY plasma concentrations were similar to those of fed animals (317 +/- 39 pmol/L). PYY infusion resulted in a dose-dependent increase in water and electrolyte absorption at all doses in both the jejunum and ileum. Although the relative increase in absorption was similar, the magnitude was greater in the ileum. CONCLUSIONS: Physiological concentrations of PYY produced an increase in small bowel absorption of water and electrolytes in vivo. The postprandial release of PYY may mediate the increase in absorption following a meal. Such a proabsorptive agent may have considerable potential for clinical use in malabsorptive states.

Animals↗

PubMed1993

Small intestinal growth caused by feeding red kidney bean phytohemagglutinin lectin to rats.

BACKGROUND: Plant lectins are present in significant quantity in a variety of food sources. The aim of this study was to determine if they stimulated growth of the intestine. METHODS: Germ-free and conventional rats were pair fed purified phytohemagglutinin lectin (PHA) or equivalent casein in a fully nutritious diet. PHA was instilled into in situ jejunal and ileal loops. Organ weight, length, DNA, protein content, morphometry, and [3H]thymidine uptake into jejunal crypt cells were measured. RESULTS: A trophic response occurred in the small intestine (jejunum greater than ileum) because of PHA (P < 0.001), was sustained by continued exposure, and was reversible on reinstitution of the control diet (P < 0.05). The intestinal microbial flora in conventional animals that were fed PHA augmented the growth-stimulatory effects of PHA on intestinal weight (P < 0.01). PHA caused fecal protein, fat, and mucous glycoprotein levels (P < 0.001) to increase in germ-free animals. PHA increased jejunal mucosal crypt depth and crypt mitotic activity (P < 0.05); DNA content (P < 0.05) and [3H]thymidine uptake (P < 0.01) into crypt cells was increased. No increase in plasma or tissue content of gastrin, enteroglucagon, or peptide YY was observed on PHA exposure, and there was no increase in organ weight of the liver, kidney, or colon. CONCLUSIONS: PHA stimulated growth of rat small intestine when present in the diet or instilled in the bowel lumen.

Animals↗

PubMed1993

Is profound peripheral insulin resistance in patients with pancreatic cancer caused by a tumor-associated factor?

Diabetes in patients with pancreatic cancer occurs in 70% to 80% of the patients and is characterized by high plasma levels of insulin. In type II diabetes that is not associated with pancreatic cancer, peripheral insulin resistance and impaired muscle glycogen synthesis are major pathogenic factors. We investigated peripheral insulin sensitivity in patients with pancreatic cancer before and after tumor removal. The effects of pancreatic tumor extracts on glycogen synthesis in skeletal muscle in vitro and the tumor content of pancreatic islet hormones were also investigated. Marked peripheral insulin resistance was found in the patients with pancreatic cancer and was more pronounced in the diabetic patients than in the nondiabetic patients. Insulin sensitivity was not correlated with weight loss, tumor size, or bilirubin levels but improved after surgery. Tumor extracts from diabetic patients with pancreatic cancer caused a marked reduction of glycogen synthesis in skeletal muscle in vitro. All tumors contained islet hormones but not in concentrations sufficient to explain the effect on glycogen synthesis. These findings indicate that a diabetogenic factor associated with pancreatic adenocarcinomas could be involved in the development of the profound peripheral insulin resistance and thereby could contribute to the high incidence of diabetes observed in patients with pancreatic cancer.

Aged↗

PubMed1993

Abnormal plasma gut hormones in pathologic duodenogastric reflux and their response to surgery.

Fasting and postprandial plasma levels of the gut hormones gastrin, cholecystokinin (CCK), secretin, glucose-dependent insulinotropic polypeptide, motilin, neurotensin, peptide YY (PYY), enteroglucagon, glucagon, insulin, and pancreatic polypeptide were measured in 11 patients with alkaline gastritis associated with excessive duodenogastric reflux not related to previous gastric surgery (primary DGR), 12 primary DGR patients after pancreatico-biliary diversion ("duodenal switch" procedure), and in 10 age-matched healthy controls. Gastric emptying of a semisolid oatmeal was also measured in patients with primary DGR and in patients after bile diversion. Fasting plasma levels of the distal gut hormone neurotensin and the pancreatic islet hormone insulin were significantly greater in patients with primary DGR compared with controls. Neurotensin levels were normal in patients studied after bile diversion. Postprandial plasma levels, incremental integrated and total integrated responses for CCK, secretin, insulin, neurotensin, PYY, and enteroglucagon, were significantly greater in patients with primary DGR compared with controls. The majority of these responses normalized after bile diversion; however, the postprandial response for insulin and enteroglucagon remained elevated. Patients with primary DGR had a rapid early postprandial phase of gastric emptying of solids, which showed a significant correlation with plasma neurotensin levels. Bile diversion produced a significant delay in this lag-phase of gastric emptying. These abnormalities in gut regulatory hormones appear to be adaptive changes to rapid early postprandial gastric emptying, probably related to antropyloric dysmotility, which has been implicated in the pathogenesis of this condition. Measurement of these gastrointestinal hormones may become useful in the diagnosis of primary DGR.

Anastomosis, Roux-en-Y↗

PubMed1993

Effects of high fat diet and cholecystokinin receptor blockade on pancreatic growth and tumor initiation in the hamster.

The mechanism by which high-fat diet potentiates pancreatic cancer is not known, but trophic hormones may be involved. In preliminary growth studies, hamsters fed a high fat diet (17.5% lard, 17.5% corn oil) for 14 days showed a 16.3% increase (P < 0.01) in pancreatic weight compared to controls on low fat diet (2.5% lard, 2.5% corn oil). A significant increase was also seen at 28 days. Similar increases were seen in pancreatic DNA (29%, P < 0.01) and pancreatic RNA (22%, P < 0.05) at 14 days. Plasma cholecystokinin (CCK) levels at 14 days were 2.5 fold higher in the animals fed high fat (P < 0.01). Infusion of the CCK antagonist MK329 (25 nmol/kg/h) completely abolished the increase in pancreatic weight, pancreatic DNA and pancreatic RNA. The effect of CCK receptor blockade during the initiation period of carcinogenesis was investigated in hamsters fed the same diets used in the growth studies. One hundred animals received a single injection of N-nitrosobis(2-oxopropyl)amine, (BOP, 20 mg/kg). Half of the hamsters in each diet group received a 2 week infusion of MK329 (25 nmol/kg/h), beginning 8 days before carcinogen administration. At the time of death, 55 weeks after carcinogen administration, non-fasting plasma CCK levels were 31% higher in the high fat fed hamsters than in the low fat fed animals (P < 0.01). The high-fat diet group had a 3-fold increase in total cancer incidence and a 5-fold increase in advanced lesions (adenocarcinomas). Tumor incidence and yield were not changed in either diet group by CCK-receptor blockade during the initiation period. Cholecystokinin appears to mediate the short-term trophic effect that high-fat feeding has on the pancreas. However, potentiation of pancreatic cancer by high-fat diet in the hamster cancer model does not appear to be influenced by endogenous cholecystokinin at the time of tumor induction.

Animals↗

PubMed1993

Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon.

Peptide YY (PYY) and enteroglucagon are hormonal peptides found in endocrine cells of the distal intestinal mucosa. Although it is known that plasma concentrations of both peptides increase in response to feeding, the mechanism by which ingested food causes release of colonic hormones is not understood. The release of PYY and enteroglucagon was measured in response to intraluminal stimuli in 176 patients having investigative colonoscopy. Introduction of air, saline (isotonic and hypertonic), glucose (isotonic and hypertonic), oleic acid (without bile salts), and casein hydrolysate all failed to release PYY but glucose caused a small but significant increase in enteroglucagon concentrations. In contrast with the lack of effect of nutrients, infusion of deoxycholic acid produced a rapid and marked dose responsive increase in plasma PYY concentrations when introduced into the sigmoid colon. PYY release was statistically significant at doses between 3.3 mM to 30 mM; for example 10 mM deoxycholate caused a sixfold increase in plasma PYY concentrations. Infusion of 10 mM deoxycholate into the transverse colon or caecum produced an increase of PYY that was similar to the responses in the sigmoid colon. There was also a significant release of enteroglucagon in response to infusion of this bile salt into the sigmoid colon at doses between 3.3 mM and 30 mM. The enteroglucagon response to 10 mM deoxycholate was similar in all three colonic regions. When oleic acid was added to deoxycholate as an emulsion, the release of PYY and enteroglucagon was similar to that seen with the bile salt alone. These findings suggest that bile salts may play an important part in the control of colonic endocrine function and may explain the increased circulating concentrations of colonic regulatory peptides that are seen in malabsorption states and after small bowel resection in humans.

Aged↗

PubMed1992

Cholecystokinin inhibits DNA alkylation induced by N-nitrosobis (2-oxopropyl)amine (BOP) in hamster pancreas.

Cholecystokinin (CCK) inhibits pancreatic cancer but not hepatic tumor induction by N-nitrosobis (2-oxopropyl) amine (BOP) in hamsters when administered with or shortly before BOP. In this study, we evaluated the capability of sulfated CCK-8 to inhibit DNA alkylation in the hamster pancreas. We examined the pattern of O6-methylguanine (G6-Me) and N7-methylguanine (G7-Me) in pancreatic ductal, acinar and liver tissues from Syrian hamsters treated with a single dose of BOP (20 mg/kg s.c.) and with five s.c. injections of CCK-8 (200 pM/kg, 30 min apart). The first CCK injection was given either 90 min before, or together, or 3 h after POP administration. The amount of G6-Me in liver DNA did not differ significantly. We observed a decrease of G7-Me in the liver of the group treated with CCK together with POP as compared to POP alone (P less than 0.005). Lower amounts of G6-Me were found in ductal preparations (P less than 0.01) of the animals treated with CCK before POP as compared to POP alone. CCK also modified the pattern of alkylation in the acinar tissue, but without a clear relationship with the timing of administration. The results suggest that the inhibitory effect of CCK-8 on pancreatic carcinogenicity of BOP could be related to its capability to modify DNA alkylation by yet unknown mechanisms.

Alkylation↗

PubMed1992

Effect of meal composition and sham feeding on duodenojejunal motility in humans.

The disruptive effect of meals of different fat content and caloric value and of sham feeding on the interdigestive migrating motor complex (IDMMC) was studied in eight healthy subjects using an ambulatory recording system that allowed continuous monitoring of small bowel motility for three consecutive days. The durations of fed pattern were not significantly different between meals of 800 kcal/50% fat, 400 kcal/50% fat, and 800 kcal/25% fat, but were significantly longer compared to IDMMC cycle length and sham feeding. The latter two were not significantly different. On a separate day, five subjects consumed a meal of 400 kcal/9% fat and a second one of 800 kcal/50% fat. The duration of the fed pattern following the high fat meal was significantly longer than the low fat one. Sham feeding significantly increased plasma concentrations of gastrin and neurotensin (NT), but did not affect those of cholecystokinin (CCK), insulin, and peptide YY (PYY). The various variables of the IDMMC were not different during the two nights of the study, and velocity of migration of phase III during the first day and both nights was similar. We conclude that the duration of the fed pattern depends, in part, on the composition of the meal. Sham feeding, resulting in an increase in both plasma gastrin and NT concentrations, does not disrupt the IDMMC. When using thin probes, IDMMC is stable during prolonged recording.

Adult↗

PubMed1992

Effect of duodenal switch procedure on gastric acid production, intragastric pH, gastric emptying, and gastrointestinal hormones.

The duodenal switch operation preserves the pylorus and the proximal 3 to 7 cm of duodenum in continuity with the stomach while diverting pancreaticobiliary secretions. We compared it with the Roux-en-Y without vagotomy or antrectomy in 12 dogs with innervated gastric pouches. Acid secretion was inhibited between tests using ranitidine in the Roux-en-Y group only, but two of the six dogs still developed stomal ulcers and the remainder showed stomal hyperemia. This may be due to a significant increase in gastric acid output after Roux-en-Y, but gastric emptying and plasma gastrin, cholecystokinin, secretin, gastric inhibitory polypeptide, peptide YY, and neurotensin were similar after both procedures. In 12 patients and a further 6 dogs, the duodenal switch caused no significant change in the intragastric pH environment as assessed by intragastric pH monitoring. The duodenal switch is a suitable procedure for pancreaticobiliary diversion.

Anastomosis, Roux-en-Y↗

PubMed1992

Neuropeptide release from the isolated, perfused, lower esophageal sphincter region of the rabbit and the effect of vasoactive intestinal peptide on the sphincter.

BACKGROUND: The aim was to evaluate the isolated, vascularly perfused, lower esophageal sphincter (LES) as a model for investigating the functional role of neuropeptides such as vasoactive intestinal peptide (VIP). METHODS: At laparotomy the LES was removed along with the distal esophagus, stomach, and left gastric artery and vein. The LES area, isolated from the body of the stomach by a custom-made clamp, was perfused with oxygenated Krebs-Ringer bicarbonate solution (pH 7.4, 38 degrees C) via the left gastric artery. The LES pressure was monitored continuously with a custom-made Dent sleeve catheter. LES pressure and release of neuropeptides were investigated after carbachol and VIP were administered alone or in combination. VIP, calcitonin gene-related peptide (CGRP), and somatostatin were measured in the venous perfusate collected from the left gastric vein. RESULTS: LES tone and contraction frequency were similarly increased by 10 and 100 nmol/L carbachol (increment, 4.0 +/- 0.26 mm Hg with 10 nmol/L carbachol; p less than 0.0003). Perfusion with 10 nmol/L VIP decreased basal tone and completely abolished the contraction induced by 100 nmol/L carbachol. VIP, CGRP, and somatostatin were released from the LES in response to 10 nmol/L carbachol (VIP rose from 55 +/- 13 to 179 +/- 24 pmol/L, CGRP, from 114 +/- 30 to 239 +/- 33 pmol/L, and somatostatin from 15 +/- 2 to 27 +/- 4 pmol/L; all p less than 0.001). CONCLUSIONS: These findings support a role for VIP in the inhibitory reflex of the LES but suggest that other neuropeptides may also be involved. The isolated, perfused LES provides a new tool for investigating neuropeptide interactions.

Animals↗

PubMed1991

Adaptive increase in peptide YY and enteroglucagon after proctocolectomy and pelvic ileal reservoir construction.

Functional results improve with time after proctocolectomy and pelvic ileal reservoir construction. We hypothesized that adaptive increases of circulating and tissue levels of the gut hormones peptide YY (PYY) and enteroglucagon may contribute to this improvement by slowing small bowel transit and increasing small bowel absorption. The specific aim of this study was to measure plasma and ileal mucosal concentrations of PYY and enteroglucagon in dogs 1 year after proctocolectomy and ileal reservoir-anal anastomosis. In the ileal reservoir dogs, postprandial PYY levels reached 238 +/- 31 pmol/liter compared with 93 +/- 33 pmol/liter in sham operated controls (P less than 0.001). Postprandial plasma enteroglucagon levels reached 199 +/- 53 pmol/liter in reservoir animals and 52 +/- 4 pmol/liter in controls (P less than 0.05). Tissue levels of PYY in the mucosa of the ileal reservoirs were 419 +/- 43 pmol/g compared with 133 +/- 23 pmol/g in normal terminal ileum (P less than 0.0001). Enteroglucagon levels were also elevated in reservoir mucosa (193 +/- 21 pmol/g vs. 113 +/- 9 pmol/g in controls, P less than 0.05). These data demonstrate that postprandial and tissue levels of PYY and enteroglucagon increase in dogs 1 year after construction of ileal reservoirs. The adaptive increase in PYY would slow small bowel transit and the increase in enteroglucagon would promote mucosal growth, each contributing to the improved functional results.

Adaptation, Physiological↗

PubMed1991

Distribution and immunocytochemical colocalization of peptide YY and enteroglucagon in endocrine cells of the rabbit colon.

Peptide YY (PYY) is 36 amino acid peptide hormone present in high concentrations in the colon where it is colocalized with enteroglucagon in L cells. A selective release of PYY and enteroglucagon from the rabbit colon has been described, raising the question of the exact localization of the two hormones in the rabbit colon. We have therefore examined the distribution of PYY and enteroglucagon as well as somatostatin in the rabbit colon using RIA and electron microscopic immunocytochemistry. PYY and enteroglucagon were present in high concentrations in the colorectal mucosa with peak concentrations in the left colon (PYY 544 +/- 87 pmol/g, enteroglucagon 152 +/- 10 pmol/g). Electron microscopic examination of the colonic mucosa demonstrated a large population (65%) of EC cells, a moderate population (30%) of L cells, and a small population (5%) of D cells. By immunogold labeling serotonin was localized to EC cells, PYY and enteroglucagon to L cells, and somatostatin to the D cell. Double immunogold labeling revealed PYY and enteroglucagon in all L cells examined (93 cells). A majority of the secretory granules (83%) were labeled by both PYY and glucagon antibodies, whereas a significant portion of granules (15%) was labeled by the PYY antibodies alone. The results demonstrate that L cells are the sole source of PYY and enteroglucagon in the rabbit colon and that L cells contain different populations of secretory granules. The existence of different secretory granules in L cells may explain the selective release of PYY and enteroglucagon observed in the rabbit colon.

Animals↗

PubMed1991

Short-chain fatty acid release of peptide YY in the isolated rabbit distal colon.

Short-chain fatty acids (SCFAs) form the major ionic fraction of stool, provide the major metabolic substrate for colonic epithelium, and promote mucosal ion transport. Despite this prominent role of SCFAs in metabolism of the colon, their effect on colonic endocrine cell function has not been studied. Consequently, we hypothesized that SCFAs might modulate release of peptide YY (PYY) from colonic type-L endocrine cells. The specific aims of this study were to measure release of PYY from the isolated perfused rabbit distal colon stimulated by intraluminal infusion of 0.9% saline, acetate (10 mM), acetoacetate (10 mM), n-butyrate (1, 3.3, 10, 100 mM), and pyruvate (10 mM). PYY levels were measured by radioimmunoassay in the venous effluent of the rabbit colon. All four SCFAs (10 mM) caused at least a twofold increase in integrated release of PYY from the isolated perfused rabbit colon. Graded concentrations of n-butyrate caused a stepwise release of PYY. This study suggests that SCFAs may modulate the release of colonic PYY in rabbits.

Acetates↗

PubMed1990

Significance of gastric endocrine tumor and age-related gut peptide alterations in Mastomys.

The Mastomys (Praomys natalensis) species are a unique natural model in which the bioactivity of gastric carcinoids may be studied. Several investigators have previously demonstrated that these tumors contain large amounts of histamine. In this study we investigated the presence of peptides associated with the neoplasm. The levels and location of gastrin, gastric inhibitory peptide (GIP), neurotensin, peptide YY (PYY), pancreatic polypeptide (PP), glucagon, bombesin, vasoactive intestinal peptide (VIP) and somatostatin (SRIF) were investigated by radioimmunoassay and immunocytochemistry. In addition the distribution of these peptides were evaluated in the gastrointestinal tract of young and old animals to investigate possible age-related changes. PYY and enteroglucagon (EG) were significantly (P less than 0.001) elevated in both tumor tissue (676 +/- 152, 551 +/- 164 pmol/g) and plasma (620 +/- 160, 500 +/- 147 pmol/l) of tumor-bearing animals. Immunocytochemistry revealed PYY- and EG-like immunoreactivity in 20-30% of tumor cells. A significant decrease (P less than 0.05) in bombesin was noted in older animals, but no changes in gastric tissue content of PYY or EG could be detected between young and old animals. Gastrin was not detected in tumors and there were no significant changes in tissue or plasma levels with age. Small bowel concentrations of VIP and PYY were higher in the older mastomys (P less than 0.05). In contrast, colonic levels of bombesin, VIP, somatostatin and PYY were significantly lower (P less than 0.05) in older mastomys compared with young. The age-related changes in several peptides may reflect an adaptive response to acid hypersecretion. The multi-hormonal character of these neoplasms suggests that these tumors develop from a pluripotential stem cell.

Age Factors↗

PubMed1990

Amelioration of cholinergic-induced pancreatitis with a selective cholecystokinin receptor antagonist.

Acute edematous pancreatitis follows excessive cholinergic stimulation in patients exposed to anticholinesterase-containing insecticides. We describe the role of cholecystokinin and the benefits of cholecystokinin receptor blockade in this form of pancreatitis. A cholinergic mimetic (carbachol) was administered to rats weighing 300 to 350 g and produced a form of edematous pancreatitis that mimics that seen in humans. Animals received carbachol intraperitoneally, either alone (250 micrograms/kg of body weight) or with cholecystokinin-receptor antagonist devazepide (3 mg/kg of body weight) and were killed 4 hours later. Carbachol administration resulted in a 19% increase in pancreatic weight, a fourfold increase in serum amylase levels, and a 14-fold increase in serum lipase levels. Plasma cholecystokinin levels, however, were not altered. Devazepide administered prior to cholinergic hyperstimulation blocked pancreatic weight increase and reduced elevations in serum amylase levels twofold and lipase levels fourfold. Although cholecystokinin levels are not elevated in this model of pancreatitis, blockade of even low, background concentrations of this regulatory peptide is beneficial.

Acute Disease↗